CYTOBLASTIN 1MG INJECTION

Indications

• Hodgkin's lymphoma
• Non-Hodgkin's lymphoma
• Testicular cancer
• Breast cancer
• Soft tissue sarcomas
• Choriocarcinoma
• Other malignancies

Dosage

Adults: Refer to the BNF for specific dosing guidelines based on the

Mechanism of action

Vinblastine exerts its antitumor effects mainly by inhibiting mitosis at the metaphase stage. It interacts with tubulin, a key protein in the mitotic spindle, leading to the crystallization of microtubules. This crystallization prevents proper polymerization of microtubular proteins, causing metaphase arrest and subsequent cell death. Additionally, vinblastine impacts nucleic acid and protein synthesis and interferes with amino acid metabolism, particularly blocking the utilization of glutamic acid, which inhibits purine synthesis and affects the citric acid cycle. It also displays some immunosuppressive properties.

Pharmacodynamics

As a vinca alkaloid, vinblastine demonstrates a specific action on the cell cycle, primarily affecting the mitotic phase. Its structure consists of multiringed units derived from vindoline and catharanthine. The drug's antitumor properties are associated with its ability to induce marrow suppression and exert antileukemic effects. Vinblastine’s unique mechanism differentiates it from other antineoplastic agents, contributing to its use in combination chemotherapy regimens.

Pharmacokinetics

Vinblastine is typically administered intravenously and is distributed widely throughout the body. It has a variable half-life, ranging from several hours to days, depending on individual patient factors and dosing regimens. The drug is primarily metabolized in the liver, with renal excretion playing a minor role in its elimination. The pharmacokinetic profile can be influenced by various factors, including the presence of other medications and the patient's overall health.

Adverse effects

• Bone marrow suppression
• Nausea and vomiting
• Alopecia
• Constipation
• Peripheral neuropathy
• Mucositis
• Fatigue
• Abdominal pain

Interactions

• mitotane+vinblastine: Unknown (decreases exposure)
• rifampicin+vinblastine: Unknown (decreases exposure)
• stjohn’swort+vinblastine: Unknown (decreases exposure)

Precautions

• Use with caution in patients with existing bone marrow suppression
• Monitor for signs of infection due to immunosuppressive effects
• Caution in patients with liver impairment due to altered metabolism

Pregnancy

Vinblastine is not recommended during pregnancy due to potential teratogenic effects.

Breast-feeding

Breastfeeding is not recommended during treatment with vinblastine due to the potential for adverse effects in the nursing infant.

Storage

Store at room temperature, away from light and moisture. Keep out of reach of children.

Formulations

• Vinblastine sulfate injection

Mechanism of action

The antitumor activity of vinblastine is thought to be due primarily to inhibition of mitosis at metaphase through its interaction with tubulin. Vinblastine binds to the microtubular proteins of the mitotic spindle, leading to crystallization of the microtubule and mitotic arrest or cell death. Although the mechanism of action has not been definitely established, vinblastine appears to bind to or crystallize critical microtubular proteins of the mitotic spindle, thus preventing their proper polymerization and causing metaphase arrest. In high concentrations, vinblastine also exerts complex effects on nucleic acid and protein synthesis. Vinblastine reportedly also interferes with amino acid metabolism by blocking cellular utilization of glutamic acid and thus inhibits purine synthesis, the citric acid cycle, and the formation of urea. Vinblastine exerts some immunosuppressive activity. Experimental data indicate that the action of vinblastine sulfate is different from that of other recognized antineoplastic agents. Tissue-culture studies suggest an interference with metabolic pathways of amino acids leading from glutamic acid to the citric acid cycle and to urea. In vivo experiments tend to confirm the in vitro results. A number of in vitro and in vivo studies have demonstrated that vinblastine sulfate produces a stathmokinetic effect and various atypical mitotic figures. ... Studies indicate that vinblastine sulfate has an effect on cell-energy production required for mitosis and interferes with nucleic acid synthesis. The mechanism of action of vinblastine sulfate has been related to the inhibition of microtubule formation in the mitotic spindle, resulting in an arrest of dividing cells at the metaphase stage. Reversal of the antitumor effect of vinblastine sulfate by glutamic acid or tryptophan has been observed. In addition, glutamic acid and aspartic acid have protected mice from lethal doses of vinblastine sulfate. Aspartic acid was relatively ineffective in reversing the antitumor effect.

Pharmacodynamics

Vinblastine is a vinca alkaloid antineoplastic agent. The vinca alkaloids are structurally similar compounds comprised of 2 multiringed units: vindoline and catharanthine. The vinca alkaloids have become clinically useful since the discovery of their antitumour properties in 1959. Initially, extracts of the periwinkle plant (<i>Catharanthus roseus</i>) were investigated because of putative hypoglycemic properties, but were noted to cause marrow suppression in rats and antileukemic effects <i>in vitro</i>. Vinblastine has some immunosuppressant effect. The vinca alkaloids are considered to be cell cycle phase-specific.